The present invention relates to the use of pharmacologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives, and their acid addition salts. The compounds of this invention are ligands for serotonin receptor subtypes, especially the 5HT1A receptor, and are therefore useful in the treatment of disorders that can be treated by altering (i.e., increasing or decreasing), serotonin mediated neurotransmission.
The pharmacologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives of the formula I, as defined below, are also ligands for dopamine receptor subtypes, especially the dopamine D4 receptor. They are useful in treating conditions or disorders, schizophrenia for example, that can be treated by altering (i.e., increasing or decreasing) dopamine mediated neurotransmission. The dopamine receptor binding activity of these compounds is described in more detail in U.S. Ser. No. 08/809,145, supra, now U.S. Pat. No. 5,852,031. This application (Ser. No. 08/809,145) is incorporated herein by reference in its entirety.
Serotonin plays a role in several psychiatric disorders, including anxiety, Alzheimer's disease, depression, nausea and vomiting, eating disorders, and migraine. (See Rasmussen et al., “Chapter 1. Recent Progress in Serotonin (5HT)1A Receptor Modulators”, in Annual Reports in Medicinal Chemistry, Section I, 30, pp. 1–9, 1995, Academic Press, Inc.; Antigas et al., Trends Neurosci., 19 (9), 1996, pp. 378–383; and Wolf et al., Drug Development Research, 40, 1997, pp. 17–34. ) Serotonin also plays a role in both the positive and negative symptoms of schizophrenia. (See Sharma et al., Psychiatric Annals., 26 (2), February, 1996, pp. 88–92. )